Asthma is traditionally considered a syndrome of chronic airway inflammation. While the airways are certainly involved, there is increasing recognition of the significance of parenchymal abnormalities in asthma as well. The lung parenchyma is an important determinant of pulmonary function because the airways and parenchyma is an important determinant of pulmonary function because the airways and parenchyma are intimately related . For airway muscle to constrict and narrow the airway, it must not only act against the surrounding tethering forces provided by parenchymal attachments. Likewise, for the parenchyma to stabilize airway caliber, there must exist an effective mechanical link between the airway and parenchyma. This proposal addresses three issues involved in the airway-parenchymal mechanical interactions involved in asthma. First, we will determine the extent to which increased tissue resistance and elastance (stiffness) is due to heterogeneous airway closure. To do this we will study three groups of subjects: normals, mild, asthmatics, and moderate-to-severe asthmatics. After measurement of standard pulmonary function, we will measure input impedance by means of forced oscillations, both in the whole lung as well as at the level of the bronchoscopically wedged subsegment. Impedance measurements reflect the physical properties of both the airways and tissue, and these specific properties can be determined from mathematic modeling. Airway closure will be simultaneously assessed by means of high resolution computer tomography of the lung. Finally, the acute responses of impedance and imaging that occur following the acute effects of deep inhalation and changes in lung volume. We will further relate airway wall stiffness to airway inflammation by measuring inflammatory indices in induced sputum. Third, we will determine the physiologic effects and site of action of inhaled steroids. This information is important for determining whether this pharmacological approach is adequate for treating both the airway and parenchymal abnormalities in asthma. Together, these experiments will enhance our understanding of the mechanisms involved in altered airway-parenchymal mechanics in asthma, and will provide a unique basis for developing new modes of therapy.